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Strategies for Antidepressant-Resistant Depression

Am Fam Physician. 2002 Jun 1;65(11):2373.

Approximately 40 percent of patients with depression do not respond to the initial trial of antidepressants. This creates a dilemma for physicians because there are no studies that demonstrate if it is better to switch medications within the same class or switch to another class for these patients. Currently, the selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressants (TCAs) are the most widely prescribed anti-depressants. Thase and associates studied the effectiveness of SSRIs and TCAs in the treatment of antidepressant-resistant chronic depression.

The study was a multicentered, collaborative research program studying chronic depressive disorders. Patients who met criteria in the Diagnostic and Statistical Manual of Mental Disorders(DSM-III, revised) for chronic major depressive disorder or double depression were eligible for the study and were divided into two groups. Group 1 was treated with imipramine in a dosage of 50 mg per day, titrated by 50 mg per day, as tolerated, every week until response or the maximum dosage of 300 mg per day was obtained. Group 2 was treated with sertraline in a dosage of 50 mg per day that was, after week 3, titrated by 50 mg per day each week until response or the maximum of 200 mg per day was obtained.

After 12 weeks, the nonresponders were identified, tapered off their medications, and assigned to a washout period. Patients in group 1 who were nonresponsive to imipramine were then started on the sertraline protocol, while patients in group 2 who were nonresponsive to sertraline were started on the imipramine protocol. This process was done in a blinded fashion. After 12 weeks, participants were reassessed to determine their response to the treatment protocol.

The switch from imipramine to sertraline and from sertraline to imipramine provided clinical and statistically significant improvements in the two groups. The patients switched from imipramine to sertraline experienced fewer adverse effects. The sertraline group had a higher response rate in the intent-to-treat samples, but a more comprehensive, generalized equation analysis of continuous dependent measures showed no difference between the two treatment groups.

The authors conclude that more than 50 percent of the chronically depressed antidepressant nonresponders in their study benefited from a switch from imipramine to sertraline or vice versa. This benefit occurred despite a high degree of chronicity of depression. Switching from one class of antidepressants to another can be a useful treatment strategy in patients who do not respond to the initial medication trial.